Fumonisin toxicity in a transgenic mouse model lacking the mdr1a/1b P-glycoprotein genes.

The toxicity of fumonisin B(1) (FB(1)) was investigated in male mdr1a/1b double knockout (MDRK) mice, lacking the drug-transporting P-glycoproteins. These transgenic animals are deficient in their blood:brain barrier and accumulate different drugs in brain and other tissues. The MDRK and their wild-type counterparts, FVB mice, were injected subcutaneously with 2.25 mg/kg per day of FB(1) for 5 days and sampled one day after the last treatment in a protocol that has resulted in marked hepatic and renal damage in other strains. FB(1) caused liver enlargement in both FVB and MDRK. Hematological parameters were not affected in either strain. Plasma levels of alanine aminotransferase and aspartate aminotransferase, measures of liver damage, were increased by FB(1) in both FVB and MDRK mice. Histopathological evaluation of liver corroborated this finding. Kidney lesions were induced by FB(1) in both types of mice. Concentrations of free sphingosine and sphinganine increased in liver and kidney of both strains after the FB(1) treatment, although the increase in liver sphingoid bases was half as much in MDRK as compared to FVB. The levels of sphinganine-containing complex sphingolipids were increased in kidney. The levels of sphingosine-containing complex sphingolipids in kidney were unaffected by FB(1) treatment but were significantly lower in control MDRK than in FVB mice. The levels of neurotransmitters and their metabolites were similarly affected in both strains by FB(1), suggesting no influence of disrupted blood:brain barrier on FB(1)-induced neurotoxicity. In both strains, the liver mRNA for tumor necrosis factor alpha was increased; however, the increase was statistically significant only in FVB. It was apparent that mice deficient in P-glycoprotein do not exhibit greater sensitivity to FB(1), the cellular or brain transport of FB(1) appears to be independent of this multidrug transporting system.

Phase transitions in the incoherent lattice fluctuations in YBa2Cu3O(7-delta)

The growing body of experimental evidence for the existence of complex textures of charges and spins in the high-temperature superconductors has drawn attention to the so-called 'stripe-phase' models as a possible basis for the mechanism of superconductivity in these materials. Such observations have until now been restricted to systems where the texture dynamics are slow or suppressed altogether, and do not include the important case of YBa2Cu3O(7-delta). It seems likely that the dynamic behaviour of stripes, which has been suggested to undergo several phase transitions as a function of temperature, should also be reflected in the lattice properties of the host materials, and this forms the motivation for our present experiments. Specifically, we use MeV helium ion channelling, an ultrafast real-space probe of atomic displacements (with sub-picometre resolution), to probe incoherent lattice fluctuations in YBa2Cu3O(7-delta) as a function of temperature and oxygen doping. We detect lattice fluctuations that are larger than the expected thermal vibration component, and which show anomalies characteristic of the phase transitions anticipated for a dynamic stripe phase. Comparison of our lattice results with single-particle-tunnelling and photoemission data highlights the importance of spin-charge separation phenomena in the copper oxide superconductors.